How does it happen?

Build up of immune complexes along the GBM –> lost of podocyte foot processes –> thickening of the GBM –> sclerosis & hyalinisation of glomeruli

membranous-immunecomplex.pngImage from UNC Kidney Centre


What is seen on light microscopy?

Thickening of the GBM with little or no cellular proliferation or infiltration. As the disease progresses – chronic sclerosing glomerular and tubulointerstitial changes develop.


Image from

Long arrows show thickened GBM compared to short arrows showing tubular wall. *=mesangial expansion


Silver stain


Image from

Arrow showing ‘spikes’ along the GBM, which are new basement membrane growing in between the sup epithelial deposits.



IF ?

Diffuse granular pattern of IgG or C3 staining along the GBM.


Image from 

Diffuse granular IgG along the capillary walls


Subepithelial electron dense deposits on the outer aspect of the GBM, effacement of the foot processes of the overlying podocyte, and expansion of the GBM by deposition of new extracellular matrix between the deposits – known as ‘spikes’.

Primary/Idiopathic Membranous

  • electron dense deposits are exclusively sub epithelial and intramembranous.
  • tubular basement membrane staining is rare
  • IgG deposits are mostly IgG4
  • Staining for PLA2R and C1q
  • Staining for IgG1 and IgG3 and leukocyte invasion of the glom tuft is more in keeping with secondary MN


Causes of MN

  1. Specific targets
    1. Transmembrane receptor expressed in podocytes
      • Phospholipase A2 Receptor Ab – PLA2R Ab
      • Thrombospondin type-1 domain containing 7A (THSD7A)
    2. Peptides expressed by podocytes
      • neutral endopeptidase (from mom to child)
    3. Abs directed against other antigens
      • IgG4 against PLA2R etc
  2. Genetics
    1. PLA2R on chromosome 2q24
    2. HLA-DQA1 on chromosome 6p21
  3. SLE
    1. Stains for IgA,M and C1q with sub endothelial and sub epithelial deposits and tubuloreticular structures in the glomerular endothelial cells
  4. Drugs
    1. Penicillamine
    2. Gold
    3. Anti TNF agents
    4. NSAIDS
  5. Infections
    1. Hepatitis B with hypocomplementanaemia
    2. Hep C but less so
    3. Syphillis
  6. Malignancy
    • mostly solid tumours – prostate/lung/GI tract
    • less commonly haematological malignancy – CLL
      • deposition of tumor antigens in the glomeruli promotes antibody deposition and complement activation, leading to epithelial cell and GBM injury, and consequent proteinuria
      • in situ binding of antibodies to podocyte antigens – THSD7A & PLA2R
  7. IgG4 disease


and lastly MN can also be seen in conjunction with:

  1. Diabetes
  2. Crescentic GN – ANCA/GBM
  3. FSGS
  4. IgA
  5. Lupus


Tests to be carried out if kidney biopsy shows MN

  1. PLA2R Ab tires
  2. Complement (should be normal in just MN, but affected in SLE/Hepatitis)
  3. ANCA/dsDNA
  4. Malignancy screen


ACEi/ARB first

IS only if nephrotic AND AT LEAST ONE OF:

  1. UPCR > 400 + 50% over baseline value that has not improved since starting ACEi/ARBs AFTER 6 months
  2. Life threatening complications with nephrotic sydrome
  3. Creat increase >30% in 6-12 months AND GFR remains 25-30 with changes not explained by superimposed complications

1st line: Treat with Ponticelli regimen :

  • 6 months
  • alternative oral/IV steroids and oral CYC (preferred) or chlorambucil
  • After 6 months, manage conservatively for another 6 months
  • Can use continuous daily oral CYC/chlorambucil

2nd line (if 1st line contra indicated or resistant):

  • CNI  – CyA /Fk
    • For at least 6 months
    • IF fail : STOP CNI
    • IF remission : decrease CNI every 4-8 weeks to 50% of starting dose and continue for 1 year

– use initial therapy that worked to achieve remission
– Ponticelli can only be repeated ONCE. Do not use more than once in children



Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s